RESUMO
INTRODUCTION: ABL2 contributes to the oncogenic potential of cancers, pointing to its inhibition as a possible strategy against malignant diseases. Bioinformatics prediction of upstream effector miR-30a-5p for ABL2 allowed us to hypothesize and then validate mechanistic actions of miR-30a-5p in lung adenocarcinoma (LUAD). MATERIALS AND METHODS: The ABL2 expression in LUAD was analyzed in the TCGA data, clinical samples, and cell lines. The shRNA-mediated silencing of ABL2 was introduced to illustrate its effect on malignant phenotypes of LUAD cells. The binding affinity between ABL2 and miR-30a-5p was verified by luciferase activity and RNA pull-down assay. Ectopic expression, knockdown methods, and PI3K inhibitor LY294002 were used to investigate their effects on in vitro biological characteristics and in vivo tumor growth of LUAD cells. Using nude mouse lung adenocarcinoma in situ and brain metastasis models to validate the inhibitory effect of miR-30a-5p on LUAD by regulating the ABL2/PI3K/AKT signaling axis. RESULTS: High expression of ABL2 and poor expression of miR-30a-5p were noticed in LUAD tissues and cell lines. Importantly, miR-30a-5p was demonstrated to target and downregulate ABL2, subsequently inactivating the PI3K/AKT pathway. miR-30a-5p inhibited the malignant phenotypes of LUAD cells by inhibiting ABL2 expression and inactivating the PI3K/AKT pathway. For in vivo experiments, miR-30a-5p was substantiated to thwart tumor tumorigenesis by regulating the ABL2/PI3K/AKT axis. In addition, miR-30a-5p suppresses the occurrence and development of in situ lung cancer and brain metastasis via the ABL2/PI3K/AKT signaling pathway. CONCLUSION: This study underscores the inhibitory role of miR-30a-5p in LUAD through the ABL2/PI3K/AKT axis, which may be a viable target for LUAD treatment.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Encefálicas , Carcinoma in Situ , Neoplasias Pulmonares , MicroRNAs , Animais , Camundongos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Adenocarcinoma de Pulmão/genética , Camundongos Nus , Neoplasias Pulmonares/genética , MicroRNAs/genéticaRESUMO
Introduction: Constipation is a common clinical condition, particularly among cancer patients. Objective: To assess the prevalence and severity of CF in women with high-grade intraepithelial neoplasia (HSIL) and cervical cancer (CC), as well as the impact of this condition on their daily lives. Methods: A cross-sectional study was conducted at a tertiary cancer center. To assess the presence and severity of constipation, the Rome IV criteria, and the Constipation Scoring System (CSS) were used. To assess the impact of constipation on daily life, the Visual Analogue Scale (VAS) was used. Results: The study included 153 patients with HSIL or CC, with a median age of 44 (IQR 35-56) years. Constipation was reported in 54 (35.3%) patients, 33 (61.1%) of those with HSIL, and 21 (38.9%) of those with CC. In constipated patients, the median number of positive Rome IV criteria items was 3 (IQR 2-5). "Irregular or hard stools" was the most common complaint, affecting 41 (75.9%) of the patients. In patients with CC, the use of analgesic medications was associated with constipation (p = 0.016). There is no link between constipation and invasive cancer (p = 0.492). Constipation had a daily impact of 7.5 (IQR 4.75-9), with no relationship between VAS and clinical diagnosis (HSIL or CC) [7 (IQR 3-9) X 8 (5-9.5), p-value = 0.536] The more severe the constipation, the more disturbing it is to these women's daily lives. Conclusion: Constipation is common in women with cervical lesions, affecting their daily lives regardless of their severity. (AU)
Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma in Situ , Neoplasias do Colo do Útero , Inquéritos e Questionários , Constipação Intestinal/epidemiologia , Estadiamento de NeoplasiasRESUMO
Introduction: Anal examination and videoanoscopy (VA) are rarely performed during colonoscopies. In recent years, there has been a considerable increase in lesions of sexually transmitted anal and rectal infections, but these conditions are not noticed or reported during routine colonoscopy. Objective: To raise awareness regarding the fortuitous findings of lesions and sexually transmitted infections (STIs) in colonoscopy exams and to demonstrate that anal examination and VA provide important information and should be routinely performed. Methods: We conducted a descriptive retrospective study in 16,132 patients screened by colonoscopy and VA between 2006 and 2018. Among numerous other findings, the presence of anal condylomata and sexually transmitted retitis or perianal dermatitis was observed. The rates of each finding were calculated, and the patients were subdivided by sex and into age groups by blocks of ten years. Results: Among the 16,132 colonoscopies performed, 26 cases of condyloma (0.16%) and 50 cases of proctitis or perianal dermatitis suspicious for STI (0.33%) were found. Conclusion: Performing anal examination and VA systematically in all routine colonoscopies enabled the identification of numerous anal conditions, including several fortuitous cases of STIs. The study proposes that anal examination and VA should be performed in all routine colonoscopies and, in suspected cases, complementary tests for STIs. (AU)
Assuntos
Canal Anal/lesões , Neoplasias do Ânus/diagnóstico , Colonoscopia , Infecções por Papillomavirus/diagnóstico , Carcinoma in Situ/diagnóstico , Infecções por Papillomavirus/terapia , Dermatite de Contato/diagnósticoRESUMO
Some transcripts that are not translated into proteins can be encoded by the mammalian genome. Long noncoding RNAs (lncRNAs) are noncoding RNAs that can function as decoys, scaffolds, and enhancer RNAs and can regulate other molecules, including microRNAs. Therefore, it is essential that we obtain a better understanding of the regulatory mechanisms of lncRNAs. In cancer, lncRNAs function through several mechanisms, including important biological pathways, and the abnormal expression of lncRNAs contributes to breast cancer (BC) initiation and progression. BC is the most common type of cancer among women worldwide and has a high mortality rate. Genetic and epigenetic alterations that can be regulated by lncRNAs may be related to early events of BC progression. Ductal carcinoma in situ (DCIS) is a noninvasive BC that is considered an important preinvasive BC early event because it can progress to invasive BC. Therefore, the identification of predictive biomarkers of DCIS-invasive BC progression has become increasingly important in an attempt to optimize the treatment and quality of life of patients. In this context, this review will address the current knowledge about the role of lncRNAs in DCIS and their potential contribution to the progression of DCIS to invasive BC.
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Neoplasias da Mama , Carcinoma in Situ , Carcinoma Intraductal não Infiltrante , RNA Longo não Codificante , Animais , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Qualidade de Vida , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma in Situ/genética , Epigênese Genética , Mamíferos/metabolismoRESUMO
Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but the effectiveness of any regimen is limited and recurrence rates are high. Here, we investigated the molecular mechanisms of acquired resistance in GBC through the development and characterization of two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR). Morphological changes, cross-resistance, and migratory/invasive capabilities were evaluated. Then, microarray-based transcriptome profiling and quantitative SILAC-based phosphotyrosine proteomic analyses were performed to identify biological processes and signaling pathways dysregulated in gemcitabine-resistant GBC cells. The transcriptome profiling of parental and gemcitabine-resistant cells revealed the dysregulation of protein-coding genes that promote the enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, the phosphoproteomics analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as ABL1, PDGFRA, and LYN, which could be novel therapeutic targets in GBC. Accordingly, NOZ GemR showed increased sensitivity toward the multikinase inhibitor dasatinib compared to parental cells. Our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant GBC cells, which greatly expands our understanding of the underlying mechanisms of acquired drug resistance in GBC.
Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , Humanos , Gencitabina , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Proteômica , Linhagem Celular TumoralRESUMO
BACKGROUND: This systematic review aimed to conduct a complete investigation of the demographic aspects, clinicopathological features, degrees of epithelial dysplasia, and malignant transformation rate of actinic cheilitis. METHODS: The study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews (CRD42020201254). A search without year and language restrictions was performed using PubMed/MEDLINE, Embase, Virtual Health Library, Scopus, Web of Science, and gray literature. Studies that provided information on patients with actinic cheilitis were included, excluding those with general information on other diseases or other types of cheilitis. Risk of bias was explored using the Joanna Briggs Institute tool. Narrative and quantitative data syntheses were performed using meta-analyses and subgroup analyses. Association tests were also performed. RESULTS: Thirteen studies (728 patients) were included. The most prevalent clinical signs were dryness (99%), blurred demarcation between the lip vermilion and skin (82%), scaling (69%), and atrophy (69%). Regarding epithelial dysplasia, a prevalence of mild dysplasia (34.2%), followed by moderate (27.5%), and severe (14.9%). The malignant transformation rate was 14%. Crusts, ulcerations, and erythematous areas were associated with lip carcinoma (p < 0.001), and scaling was associated with actinic cheilitis (p < 0.001). CONCLUSIONS: This study revealed several features of actinic cheilitis, providing an overview of the disease. It is suggested that new studies help develop policy guides for the standardization of clinical criteria, enabling more rigorous and homogeneous analysis of actinic cheilitis.
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Carcinoma in Situ , Queilite , Neoplasias Labiais , Humanos , Queilite/epidemiologia , Queilite/patologia , Neoplasias Labiais/patologia , Pele/patologia , Transformação Celular Neoplásica/patologiaRESUMO
OBJECTIVE: Guidelines for treatment of non-small cell lung cancer identify patients with tumors ≤2 cm and pure carcinoma in situ histology as candidates for sublobar resection. Although the merits of lobectomy, sublobar resection, and lymphoid (LN) sampling, have been investigated in early-stage non-small cell lung cancer, evaluation of these modalities in patients with IS disease can provide meaningful clinical information. This study aims to compare these operations and their relationship with regional LN sampling in this population. METHODS: The National Cancer Database was used to identify patients diagnosed with non-small cell lung cancer clinical Tis N0 M0 with a tumor size ≤2 cm from 2004 to 2017. The χ2 tests were used to examine subgroup differences by type of surgery. Kaplan-Meier method and Cox proportional hazard model were used to compare overall survival. RESULTS: Of 707 patients, 56.7% (401 out of 707) underwent sublobar resection and 43.3% (306 out of 707) underwent lobectomy. There was no difference in 5-year overall survival in the sublobar resection group (85.1%) compared with the lobectomy group (88.9%; P = .341). Multivariable survival analyses showed no difference in overall survival (hazard ratio, 1.044; P = .885) in the treatment groups. LN sampling was performed in 50.9% of patients treated with sublobar resection. In this group, LN sampling was not associated with improved survival (84.9% vs 85.0%; P = .741). CONCLUSIONS: We observed no difference in overall survival between sublobar resection and lobectomy in patients with cTis N0 M0 non-small cell lung cancer with tumors ≤2 cm. Sublobar resection may be an appropriate surgical option for this population. LN sampling was not associated with improved survival in patients treated with sublobar resection.
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Carcinoma in Situ , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma in Situ/etiologia , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Screening of anal cancer is rarely available or performed in Brazil. This study analyzes the diagnostic performance of conventional cytology (CC) in the prevention of anal cancer in a coloproctology and gynecology outpatient clinics in a public hospital in Rio de Janeiro, Brazil. METHODS: From 2005 to 2017, 1066 conventional cytological samples were collected. We analyze the causes of unsatisfactory samples (11.3%) and compare the cytological diagnoses of 83 samples from persons living with HIV and persons not living with HIV and in specific situations, using as the gold standard high-resolution anoscopy or histopathology in cases biopsied within 6 months after cytology. RESULTS: The sensitivity of cytology with diagnosis of ASC-US for detection of anal intraepithelial neoplasia of any grade was 85%, specificity was 41%, positive and negative predictive values were 64% and 75%, respectively, and positive and negative likelihood ratios were 1.46 and 0.35, respectively. CONCLUSION: Conventional cytology available in resource-limited settings is a simple, noninvasive, low-cost method that proved feasible for outpatient screening of precursor lesions of the anal canal.
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Neoplasias do Ânus , Carcinoma in Situ , Infecções por HIV , Infecções por Papillomavirus , Humanos , Papillomavirus Humano , Brasil/epidemiologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/patologia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/patologia , Canal Anal/patologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/patologia , PapillomaviridaeRESUMO
There are few pathologic or molecular studies of penile precancerous lesions, and the majority refers to lesions associated with invasive carcinomas. Penile Intraepithelial Neoplasia (PeIN) is classified in two morphologically and distinctive molecular groups, non-HPV and HPV-related with special subtypes. The primary purpose of this international series was to classify PeIN morphologically, detect HPV genotypes and determine their distribution according to PeIN subtypes. A secondary aim was to evaluate the p16INK4a immunostaining as a possible HPV surrogate for high-risk HPV infection in penile precancerous lesions. Samples consisted of 84 PeIN cases, part of a retrospective cross-sectional analysis of 1095 penile carcinomas designed to estimate the HPV DNA prevalence in penile cancers using PCR and p16INK4a immunostaining. Penile Intraepithelial Neoplasia (PeIN) was classified in HPV-related (basaloid, warty-basaloid, warty, hybrid, and mixed subtypes) and non-HPV-related (differentiated), the former being the most frequent. PeIN subtypes were differentiated (non-HPV-related) and basaloid, warty-basaloid, warty, hybrid and mixed (HPV-related). Basaloid PeIN was the most commonly diagnosed subtype, and HPV16 was the most frequent HPV genotype detected. Warty-basaloid and warty PeIN showed a more heterogeneous genotypic composition. Most HPV genotypes were high-risk but low-risk HPV genotypes were also present in a few cases (4%). A single HPV genotype was detected in 82% of HPV positive cases. In contrast, multiple genotypes were detected in the remaining 18% of cases. The findings in this study support the paradigm that penile in situ neoplasia, like its invasive counterparts, is HPV dependent or independent and has distinctive morphological subtypes readily identified in routine practice. Considering that HPV16 is clearly the predominant type, and that the three available vaccines have HPV16, all of them will be suitable for vaccination programs; the price of the vaccines will be probably the main determinant to choose the vaccine.
Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Papiloma , Infecções por Papillomavirus , Neoplasias Penianas , Lesões Pré-Cancerosas , Neoplasias Cutâneas , Masculino , Humanos , Neoplasias Penianas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Carcinoma in Situ/patologia , Estudos Transversais , Estudos Retrospectivos , Carcinoma de Células Escamosas/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Neoplasias Cutâneas/complicações , Genótipo , Papillomaviridae/genéticaRESUMO
BACKGROUND AND OBJECTIVES: OVOL1 is a gene that negatively regulates mesenchymal transformation, which allows epithelial cells to invade the stroma. On the other hand, it negatively regulates c-Myc, which has a positive effect on cell proliferation. The aim of this study is to evaluate the expression of OVOL1 and c-Myc in ocular surface squamous neoplasia (OSSN). PATIENTS AND METHODS: Cross-sectional cohort study of 36 samples including 6 squamous papillomas, 19 conjunctival intraepithelial neoplasms, 6 squamous carcinomas and 7 normal conjunctivae were evaluated using immunohistochemistry against OVOL1 and c-Myc. The expression of both markers was analysed using the H-score (intensity 1-3 multiplied by the percentage of positive cells). RESULTS: Percentages of 98 and 100 of the OSSN, and 57 and 71% of the normal conjunctivae expressed OVOL1 and c-Myc respectively, however, the mean H-score of OVOL1 and c-Myc was higher in the OSSN than in normal conjunctivae group (P=0.0001 in both). Within the OSSN, OVOL1 demonstrated a higher H-score in the conjunctival intraepithelial neoplasms and papilloma, compared to the squamous carcinoma (P<0.01) group. c-Myc did not show differences between the OSSN groups. An H-score lower than 35 differentiates a squamous cell carcinoma from other OSSN lesions with a sensitivity of 83.3% and a specificity of 100%. CONCLUSIONS: The expression of OVOL1 is a useful tool to differentiate between a squamous carcinoma of conjunctival intraepithelial neoplasms and papilloma. OVOL1 could play a role in the invasiveness of squamous neoplasms and places it as a potential therapeutic target.